Polish researchers: frog enzymes can help, among others in the treatment of leukemias

Ribonuclease (enzymes that break down ribonucleic acid) from leopard frog cracks (Rana pipiens) can help in the treatment of currently incurable varieties of leukemia and lymphoma – research scientists from the Medical University of Lodz indicate.

Their results were presented at the 52nd annual meeting of the American Society of Hematology (ASH), which is held in Orlando, Florida (USA).

The anti-cancer ribonuclease we tested – onconase and R-amphinase, have a unique mechanism of action, different from the currently used cytostatics, whose action is directed at the DNA of the cell – told PAP the lead author of the study, Prof. dr hab. med. Piotr Smolewski, head of the Department of Experimental Hematology at the Medical University of Lodz.

Onconase and R-amphinase have been isolated in the US, the pharmaceutical company Alfacell Corporation (now Tamir Biotechnology Inc.), Somerset. One of the pioneers of this research is Dr. Wojciech Ardelt, a Polish chemist who has lived in the USA for many years.

A few years ago, Alfacell Corporation approached us with a proposal to research the possibility of using both ribonucleases in the treatment of blood cancers. At the end of 2009, we received a three-year grant for this purpose from the Ministry of Science and Higher Education – explained Prof. Smolewski.

Research is carried out on cells from patients with acute leukemia, chronic lymphocytic leukemia and multiple myeloma, as well as on cell lines from various types of malignant lymphomas.

It turned out that the tested enzymes were effective in inducing suicidal, programmed death of cancer cells (so-called apoptosis), and in some cases their effect was enhanced in combination with various routinely used anti-cancer drugs.

The strongest anti-cancer effects were seen in chronic lymphocytic leukemia (CLL), Burkitt’s lymphoma and diffuse large B-cell lymphoma (DLBCL), said the hematologist. As he explained, in the case of CLL, the combination of onconase with drugs routinely used in this disease – cladribine or fludarabine enhanced the anti-cancer effect. In Burkitt’s lymphoma, the effectiveness of each enzyme was enhanced by the addition of doxorubicin. Moreover, both drugs, even at low doses, were toxic to DLBCL lymphoma cells, and combining them with a combination of drugs currently used in the treatment of this disease (the so-called R-CHOP regimen) further increased these effects.

Our results so far seem very promising, as many cancers of the haematopoietic system still lack effective therapies. Importantly, both enzymes showed high selectivity, i.e. they only killed cancer cells and saved healthy cells – told PAP Prof. Smolewski.

The researcher also noted that these studies are currently in the preclinical phase. The next step should be to test the activity of these drugs in animal models, and then – if their anti-cancer efficacy is confirmed – in controlled clinical trials.

I am especially pleased with the results obtained on the DLBCL cell model, because it is an aggressive lymphoma, and it accounts for a third of all lymphomas. The disease is currently potentially curable in about 50-60%, but it seems that the combination of the current therapy with a very well-tolerated onconase could further increase the cure rate. Of course, this requires confirmation in further research – commented prof. Smolewski.

The research was conducted in cooperation with scientists from the Department of Hematology of the Medical University of Lodz, headed by prof. dr hab. med. Tadeusz Robak, with the team of prof. Zbigniew Darzynkiewicz, director of the Brander Cancer Research Institute, New York College of Medicine and with researchers from Tamir Biotechnology Inc. (including Dr. Wojciech Ardelt and Dr. Charles Muniz).

From Orlando Joanna Morga (PAP)

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